Introduction to Anaemia

• anaemia is the reduction in the oxygen carrying capacity of the blood due to a lower haemoglobin level than is normal for that individual
• haemoglobin is a pigment in RBC - if there is a problem producing Hb then there is a problem with the RBC
• anaemia affects all systems:

  • cardiovascular symptoms = tachycardia (increased heart rate), palpitations, angina
  • respiratory symptoms = breathlessness not on exertion
  • neuromuscular symptoms = headaches, tiredness, lightheadedness, tinnitus, loss of concentration
• anaemia can also cause

  • skin symptoms = pallor (particularly mucosal membranes - inside mouth under eyelid) nailbeds
  • gastrointestinal = nausea, constipation, diarrhoea
  • genitourinary = menstrual irregularity and loss of libido
• anaemia can be classified by the morphology of red cells:

  1. macrocytic/normochromic
  2. microcytic/hypochromic
  3. normochromic/normocytic
• normochromic cells under the microscope will have no clear area in the centre (central pallor)
• iron deficiency is the most common cause of anaemia in the world
• only a small proportion of total body iron enters or leaves the body stores on a daily basis as there is no physiological excretion of iron - 1-2mg lost each day of iron and 1-2mg gained each day of iron from the diet
• iron absorption is the sole mechanism by which iron stores are regulated
• excessive blood loss = loss of iron and a limited ability to absorb iron. common causes are GI tract bleed and menstrual loss
• iron is required for DNA synthesis, CO2 and O2 transport, growth and required by cytochrome complexes for energy production
• only a small portion of iron is obtained from the diet, most of the iron released form Hb catabolism is reutilised for new Hb production (iron life cycle)
• males have 4g of iron and females have 3.5g of iron in their body
• 75% of iron is in RBC within haemoglobin or myoglobin
• transferrin a transport protein contains 0.09% of total iron and ferritin the storage iron (liver) contains 25% of total iron
• 1-2mg of iron is absorbed from the 10-20mg available to replace daily losses with the main site of absorption being the duodenum and the upper jejunum
• dietary iron is mainly Fe3+ and is found in foods such as meats, vegetables, and fish
• the best source of iron is haem iron from RBC (red meat) then ferrous Fe2+ (inorganic) and then ferric Fe3+
• other dietary factors influence iron absorption - lower pH (citrate and ascorbate acids) promote the absorption and a higher pH (tannates phytates ad antacids) inhibits absorption
• a ferric reductase (Dcytb or D cytochrome b) in villi will reduce Fe3+ to Fe2+, which can then be transported into epithelial cells within the GI tract by divalent metal transporter (DMT1) although at this point the iron is not yet in circulation
• depending on the body requirements the Fe2+ will either be sequestered in a storage protein ferritin and be lost sloughing of villus (no Fe required) or exported across the basolateral membrane and enter the circulation (Fe required)
• ferroportin (FP-1) transports iron across the basolateral membrane - out of the epithelium and into the circulation
• hephaestin (Hp) oxidises Fe2+ to Fe3+ which binds to transferrin, each molecule can carry 2 iron ions
• all circulating iron is bound to transferrin - this serves 3 purposes

  1. renders iron soluble under physiological conditions (metal generally insoluble)
  2. prevents iron-mediated free radical toxicity (free iron produces radicals which are dangerous)
  3. facilitates transport into cells (transferrin transporter delivers iron to bone marrow)
• Haem is synthesised 85% in bone marrow and 15% in the liver
• haem is synthesised for incorporation into haemoglobin at the erythroblast stage of maturation (normoblast)
• transferrin carries iron to the marrow erythroblasts and binds to transferrin receptors (CD71) on the erythroblast surface membrane - CD71 receptor-transferrin-iron complex is incorporated into the cell by endocytosis. Fe3+ is then released from the complex and reduced to Fe2+
• Fe2+ is transported to the mitochondria by a carrier molecule and complexed with protoporphyrin IX to form haem, apotransferrin is recycled to the cell surface for further iron delivery
• iron is stored mostly in the liver as ferritin (heteropolymers of H & L protein subunits which function is to store iron) or haemosiderin (insoluble degraded ferritin)
• ferritin molecules aggregate and are engulfed by lysosomes and degraded - the end product of this process is haemosiderin
• equilibrium exists between haemosiderin and ferritin and in turn between ferritin and transferritin
• lack of mucosal iron binding by transferrin will mobilise iron from ferritin - not enough from diet will deplete stores of iron causing a negative iron balance and an iron deficiency develops
• iron deficiency develops in 3 stages:

  1. pre-latent = negative iron balance and iron stores start to decrease - hard to detect unless constantly measuring
  2. latent = iron stores diminished but anaemia not yet developed
  3. anaemic stage = anaemia develops with morphological changes in red cells
• most common cause of iron deficiency is blood loss - either through GI bleeding heavy menstruation or other causes. as 50ml of blood contains 25mg of iron (roughly a month intake)
• dietary iron deficiency is rare but many factors influence absorption - acid increasing alkaline decreasing
• gastric or intestinal abnormalities such as chrons disease, coeliac disease, gasterectomy, bowl resection can cause iron deficiency
• increased utilisation of iron through pregnancy or growth in kids and teenagers can cause iron deficiency
• symptoms of iron deficiency include:

  • pallor, fatigue, palpitations, lightheadedness - lack of O2 in transport
  • angular stomatitis (sores at corner of mouth) and/or atrophic glossitis - iron needed for mucosal enzyme system
  • koilonychia (spoon-shaped nails) - lack of iron in enzymes in the nail bed
• the laboratory diagnosis of iron deficiency from a full blood count id a reduced haemoglobin level, normal RBC count but smaller than normal in cell size
• blood film for red cell morphology in iron deficiency will show microcytic RBC and they will appear paler (with large central pallor) because they contain less haemoglobin. abnormal shapes (rod, pencil, target cells) are also found